Impairment of neutrophil function is considered as a risk factor for many infections and inflammatory diseases including the periodontal diseases. However, neutrophils have also been implicated in the pathology of many chronic inflammatory conditions. Early animal studies on induced periodontitis by ligature placement and recent reports on elevated neutrophil enzymes in gingival crevicular fluid of periodontal disease patients suggested that neutrophils may play a major role in tissue destruction in periodontal diseases. Studies on effects of cytokines on the neutrophil showed that some cytokines are capable of priming neutrophils, which means the neutrophil will exhibit enhanced responses to the subsequent stimulations after being primed. Many investigations also showed that patients with certain types of periodontal disease had hyperresponsive monocytes, which means monocytes from these patients produced high levels of inflammatory mediators upon stimulated by bacterial lipopolysaccharide, and the levels of cytokines in gingival crevicular fluid were elevated during active disease stage. This proposal is based on the hypothesis that neutrophils, in addition to their host-protective antimicrobial activity, may be primed by cytokines and other inflammatory mediators produced in the active phase of periodontal disease, and release large amount of toxic factors (granular enzymes, oxygen products) to periodontal tissues and result in tissue destruction. We further hypothesize that periodontal patients with hyperresponsive monocytes to bacterial challenge have different neutrophil functions than those with normal monocyte response. To test our hypotheses, we propose to: I) compare neutrophil functions (respiratory burst, phagocytosis and killing, release of granular enzymes, and chemotaxis) among three different periodontal disease types and insulin dependent diabetes mellitus (IDDM) patients with or without periodontal disease; 2) correlate neutrophil functions of patients with different monocytic responsiveness. The levels of cytokines in the gingival crevicular fluid will also be measured as an indicator of disease activity; and 3) determine the individual and combined effect of cytokines (IL-I, TNF-a, etc.) and other inflammatory mediatorson neutrophil functions. Thirty eight patients with different periodontal diseases and fourteen controls have been recruited to date for preliminary study. Respiratory burst, phagocytosis and killing of P. g. and A. a. were performed. No significant difference was found among different patient group. The understanding and characterization of priming of neutrophils by cytokines and other inflammatory mediators will enhance our knowledge of pathogenesis of periodontal disease, thereby providing information required to develop regimens for diagnosis, treatment and ultimately prevention of periodontal diseases.